CELLULAR LANGUAGE (II)

In Cellular Language I published recently that we tried to emphasize that big functions of the cell start up with an on-and-off switch.  The Tic and The Tan like in MORSE language, the 1and 0 of the computer.  While this is true, there are many other simple things at the molecular level that are just as simple, but full of physiologic and scientific implications.

1.ON and OFF switch:
--------------------------
 Events that lead to cancer are sometimes an exaggeration of a signal.  The K-RAS (there exist many RAS (es) as we discussed in differentiation) has a switch called the Sons of the Sevenless which can stay on, sending signals down the cell continuously.  Activated RAS will light on 3 signal pathways:
-MAP kinase (through RAF)--->FOS, JUN (stress),  MYC (the dangerous  leading to Burkitt)-TF
-RAL/CDC42 (important in the movement of the membrane, Metastasis)
-PI3K (leading to affect on AKT/MTOR) FOXO downstream hiding the PUMA-remember) 

Mutations at the RAS itself can also cause it to stay on, as opposed to knocking it out.
Remember, Mutations of RAS occur in 80% of Pancreatic cancers and 50% of colon cancer. 
Therefore, a simple switch can kill you with one of the most devastating diseases.

2. Change of shape:
---------------------
To confuse and look smart, your scientist calls this post-translational conformation to emphasize that this change has occurred later because of the nteraction with another molecule (in general).

At the surface of the membrane, there are here and there some Molecules called INTEGRINS; these are of various types and increasing molecular diversity and are best known as Receptors. They are large complexes of molecules gathered in chunks called 'subunits'.  They basically cross the thickness of the cellular membrane and,  outside the cell, they sense what is going on. Integrins serve many great purposes including cell division, proliferation, migration, adhesion to each either, differentiation, sensing etc. You name it, they do it!  Only division of DNA, this, they don't do.  But the membrane has to be divided also to make 2 cells in cell divison.   Even anti-coagulation happens here.  The versatility of the integrins is linked to the variety of subunits it is composed with.  Some are nature of cell specific and some are contact specific.  By contact specific, I mean what molecule outside the cell it will attach to (ie fibronectin Vs GPIIb).

Suffice is to say that kinking of the Integrins causes exposure of some parts of the Integrin molecule not naturally exposed.  If one looks at the skin of the joint at the back of the finger, one will see folded skin. if you forcefully bend your finger, the fold you were looking at will unfold and the bottom of the fold will come out.  This is what happen to the integrin when it meets outside the cell another molecule such as TALIN.

That bending triggers the attachment of other molecules or ions (phosphorylation) to the now exposed skin, lighting up the Integrins for the cascade of events which will unfold, including the activation of SRC in Sarcoma.
The shape imposed by the bending is also Molecule specific.  Despite the resemblance of SRC with the c-ABL (leukemia), their bending does not offer the same shape, and therefore, different parts of the molecule are exposed and 2 different diseases result.

CELL ADHESION- "join at the hip"
----------------------------------------
At many points the cells are joined to each other at the hips of the Talins.  Say,  at the hip of the Talin which linked to one Integrin, there is a PLUS SIGN at Cell A, and at the next TALIN attached to the Integrin of cell B, there is a NEGATIVE sign.  These 2 integrins will be attached, and cell adhesion is achieved.  Simple as that!

Wheels of cellular migration,
-----------------------------,
Cells can roll over other cells by progressively attaching Talin to Talins and breaking the talin-talins (integrin-integrin) behind, engulfing the integrins and using them again in the forthcoming attachment like a wheel touching the ground.  The cell is that smart at the membrane.

More simple things to come...
Hiding the PUMA behind the FOXO to have a death TRAP (Apoptsosis) in case the FOXO is compromised!
Just simple, but effective tricks ...